Foldit Puzzles

2203: Electron Density Reconstruction 13

The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model.

2202: Two-sided Strand Binder Design: Round 6

Design a beta strand and a separate protein that can bind to it! We've adjusted the H-bond Network Objective to encourage small but well-satisfied networks. We think the target strand needs just one buried, polar sidechain to achieve highly-specific binding. This puzzle allows 110 residues for the binder, and a Secondary Structure Objective will penalize designs with >50% helices. It will be important to design a binder that forms a strong beta sheet around the target strand.

2201: Monkeypox H3 Binder Design: Round 4

Design a protein that can bind to the monkeypox H3 target! AlphaFold predictions are available for your designed binder. Once you've designed a binder for the target, upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder chain only (i.e. in the unbound state, in the absence of the target). If you load this prediction, then Foldit will attempt to align the prediction with your solution (i.e. in the bound state, making an interface with the target). If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the binder interacts with the target.

2200: Revisiting Puzzle 150: Rosetta Decoy 12

This is a throwback puzzle to the early days of Foldit. This human protein helps to regulate the reduction potential of the cell, and should be modeled here in reduced form (without disulfides bonds). We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are still scientifically relevant.

2199: Two-sided Strand Binder Design: Round 5

Design a beta strand and a separate protein that can bind to it! We've adjusted the H-bond Network Objective to encourage small but well-satisfied networks. We think the target strand needs just one buried, polar sidechain to achieve highly-specific binding. This puzzle allows 100 residues for the binder, and a Secondary Structure Objective will penalize designs with >50% helices. It will be important to design a binder that forms a strong beta sheet around the target strand.

2198: Protein Design with Neural Net Mutate

This puzzle debuts the new Neural Net Mutate action! This tool uses an AI algorithm to predict a protein sequence that will fold into a give structure. Note that Neural Net Mutate does not fold sidechains like classic Mutate, so you will probably want to run Shake after mutating. Proteins designed with this AI algorithm tend to have much higher AlphaFold confidence. Read more on the Foldit blog. Or just try it out here to see what kinds of protein designs you can come up with, and how much you can increase the AlphaFold confidence!

2197: Electron Density Reconstruction 12: Round 2

Since the previous Puzzle 2191 we've adjusted the starting structure to include a residue that is absent in the deposited structure. Players may not load solutions from the Puzzle 2191. The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model.

2196: Symmetric Pentamer Design with AlphaFold Predictions

Design a symmetric protein pentamer, with 5 identical chains of 70 residues each! This puzzle enables AlphaFold predictions for the monomer subunit of your design, so you can upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your monomer subunit only (i.e. in the unbound state, in the absence of other symmetric copies). If you load this prediction, then Foldit will attempt to align the prediction with your solution. If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the monomer subunit interacts with symmetric copies.

2193: Symmetric Pentamer Design with AlphaFold Predictions

Note: This puzzle closes slightly earlier than usual, on September 7 at 16:00 UTC, due to a scheduled Foldit update

2194: Revisiting Puzzle 148: Rosetta Decoy 11

Note: This puzzle closes a day early, on September 7, due to a scheduled Foldit update.